Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice.

/pdf/germ-line-transformation-of-mice-djnya30ob2.pdf

Germ-line transformation of mice

Death of some cells in the mammalian body is clearly programmed. In the immune system there are many examples of programmed cell death, during development of lymphocytes as well as at later stages, after interaction with antigen. Many of these examples display the morphology of apoptosis: They undergo shrinkage and zeiosis, the nucleus collapses, and chromatin is cleaved into nucleosomal fragments. The cell is rapidly recognized by phagocytes and disposed of without releasing its contents. In some but not all cases of apoptosis, new macromolecular synthesis is required. Cytotoxic T cells induce changes in their targets that are morphologically apoptotic. The mechanism of apoptosis is currently under active investigation.

Apoptosis and Programmed Cell Death in Immunity

Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response

Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity.

https://www.cell.com/cell/pdf/0092-8674(88)90497-7.pdf

Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells.

Transgenic mice selectively lacking MHC class II (I-E) antigen expression on B cells: An in vivo approach to investigate la gene function

We have introduced the class II E alpha d gene into (C57BL/6 X SJL) F2 mice which do not express their endogenous E alpha gene. The mRNA expression of the E alpha d gene shows the same tissue distribution as the endogenous class II genes except in the case of one mouse, which carried 19 copies of the E alpha d gene. In this mouse expression of E alpha d mRNA was seen in all tissues tested. Expression of the transgene was induced by gamma-interferon in isolated macrophages from the transgenic mice. In addition, fluorescence activated cell sorter (FACS) analysis, mixed lymphocyte response and antigen-presentation experiments showed that the product of the transferred gene is expressed on the cell surface and functions as a major histocompatibility complex restriction element. Transmission of the gene occurred only with female transgenic mice, all males were infertile or did not transmit the gene, suggesting an effect of the transferred DNA sequence on male reproductive function.

/pdf/tissue-specific-inducible-and-functional-expression-of-the-e-1fr6bihf2s.pdf

Tissue-specific, inducible and functional expression of the E alpha d MHC class II gene in transgenic mice.

Class II genes of the MHC must be expressed by APC for activation of CD4+ T cells and efficient delivery of T cell help to B lymphocytes. Class II genes have restricted tissue expression and are under complex regulation. By using various deletion constructs of the class II E alpha d gene in transgenic mice we have mapped different 5' flanking regions which control E alpha d gene expression in distinct cell types. We demonstrate dissociate expression of E alpha d within the macrophage lineage as well as within the B cell lineage, and present evidence for a repressive element operative in B cells and macrophages. We describe the generation of novel transgenic lines with limited constitutive and inducible E alpha mRNA and I-E protein.

C. Cowing

Papers

Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells.

Transgenic mice selectively lacking MHC class II (I-E) antigen expression on B cells: An in vivo approach to investigate la gene function

Tissue-specific, inducible and functional expression of the E alpha d MHC class II gene in transgenic mice.

Selective expression of class II E alpha d gene in transgenic mice.

Tissue-specific, inducible andfunctional expression oftheEad MHC class II geneintransgenic mice